Any discussion of the background art throughout the specification should in no way be considered as an admission that such background art is prior art, nor that such background art is widely known or forms part of the common general knowledge in the field.
The pupils of the eye are often thought to only serve the function of a camera aperture, regulating the flux of light into the eye via a simple reflex mediated by parts of the mid-brain. In fact recent studies have shown that the input to the pupil system from the visual nervous system is much more complex than previously thought. This complexity is derived from the inputs from various brain areas that contribute to the pupillary response. The major site of pooling (i.e. the combination of many component signals to give a single observed response) of brain signals that contribute to the pupillary response is the pretectal olivary nucleus (PON). The two PONs then convey that information to both of the Edinger-Westphal (EW) nuclei on the two sides of the brain which in turn innervate the pupils via the oculomotor nerves. This means that each pupil receives information about the pooled activity of both retinas. Thus each pupil can independently provide information on the operation of both retinas. When a pupil gives a response to the retina of its own eye this is said to be a direct response. When a pupil responds to activity from the retina of its fellow eye that is said to be a consensual response.
About half the input to the PON is from melanopsin containing retinal ganglion cells (mcRGC) that come directly from the eye [for further information see P. D. Gamlin, “The pretectum: connections and oculomotor-related roles”, Prog Brain Res, Volume 151, Pages 379-405]. The nerve fibres of these and all the other types of retinal ganglion cells make up the optic nerve. The mcRGCs have two separate types of responses to light [for further information see D. M. Dacey, H. W. Liao, B. B. Peterson, F. R. Robinson, V. C. Smith, J. Pokorny, K. W. Yau and P. D. Gamlin, “Melanopsin-expressing ganglion cells in primate retina signal colour and irradiance and project to the LGN”, Nature, Volume 433, Pages 749-754]. The first response type derives from melanopsin that is present in the retinal bodies of these ganglion cells. Unlike the light responses of the photoreceptor cells of the retina the melanposin driven response of mcRGCs has no light adaptation mechanism and so increases steadily with increasing light level. The melanopsin pigment responds to blue light and the response itself is very slow, taking several seconds to respond to a transient increase in blue light. This slow integrative response is mainly responsible for the mean pupil size, small in the bright light, more dilated in darkness.
As with all other types of retinal ganglion cells (RGCs) the mcRGCs also convey signals derived from rod and cone photoreceptor cells of the eye. The cone driven component responds positively to yellow light (luminance) and negatively to blue light. This response type is often referred to as a Yellow-ON/Blue-OFF class of response. These responses are much more transient following the time resolution of the cones. This system also necessarily embodies the light adaptation mechanism possessed by the photoreceptors and cells that process photoreceptor information such as bipolar and horizontal cells before those signals are passed to the RGCs. Other types of retinal ganglion cells convey information to the brain about differential red and green content of images, and also the luminance (brightness) information in images. The main luminance signals are conveyed to the brain by parasol ganglion cells. The red-green colour signal is carried by midget ganglion cells. Together the parasol and midget cells make up the majority of the optic nerve fibres.
Most types of retinal ganglion cells, including parasol and midget cells, and also about half of the mcRGCs, proceed to the visual cortex via the lateral geniculate nucleus (LGN). The visual cortex is a massively interconnected set of visual processing areas. Many of these visual cortical areas are also multiply and reciprocally connected to the midbrain via the pulvinar areas [for further information see S. Shipp, “The functional logic of cortico-pulvinar connections”, Philos Trans R Soc Lond B Biol Sci, Volume 358, Pages 1605-1624; and S. Clarke, S. Riahi-Arya, E. Tardif, A. C. Eskenasy and A. Probst, “Thalamic projections of the fusiform gyrus in man”, Eur J Neurosci, Volume 11, Pages 1835-1838].
Higher centres within the extrastriate visual cortex then communicate with the PON providing about half its input nerve supply [refer to P. D. Gamlin, referenced above]. Among the various signals computed in the cortex is distance information derived from the binocular disparity between the eyes.
Another function of the pupils is the accommodative reflex by which the pupils become small when persons view objects that are close to them. Presumably this aids near vision by increasing the depth of field. Obviously the accommodative response requires information about depth and is provided to the PON by its binocular cortical inputs. The accommodative response is known to contain input from the luminance and red-green differential input systems mentioned above [for further information see F. J. Rucker and P. B. Kruger, “Accommodation responses to stimuli in cone contrast space”, Vision Res, Volume 44, Pages 2931-2944]. The spectral colour sensitivity of the human luminance system is provided by the sum of red and green sensitive cone inputs, leaving the net peak spectral sensitivity corresponding to yellow hues.
Another input to the pupil that likely derives from the visual cortex are the pupillary responses to achromatic, equiluminant, high spatial frequency patterns, which permit visual acuity to be assessed via the pupillary responses, even in children [see J. Slooter and D. van Norren, “Visual acuity measured with pupil responses to checkerboard stimuli”, Invest Ophthalmol Vis Sci, Volume 19, Pages 105-8; or K. D. Cocker and M. J. Moseley, “Development of pupillary responses to grating stimuli”, Ophthalmic Physiol Opt, Volume 16, Pages 64-67].
Therefore, the pupil has at least two possible sources of sensitivity to yellow luminance stimuli: the Yellow-ON response component of the mcRGCs and the parasol cells, the main constituents of the projection to the magnocellular layers of the LGN. The parasol RGCs have a gain control mechanism that makes them preferentially responsive to low spatial frequencies and high temporal frequencies [see E. A. Benardete, E. Kaplan and B. W. Knight, “Contrast gain control in the primate retina: P cells are not X-like, some M cells are”, Vis Neurosci, Volume 8, Pages 483-486]. The yellow-ON component of the mcRGCs does not seem to have such a gain control mechanism.
Overall, the diverse nerve supply to the pupil means that potentially it can report on the activity of a large proportion of the optic nerve fibres, and various parts of the visual thalamus and cortex. One common form of visual testing done on human subjects is characterising the extent and function of the visual fields of the eyes.
Human visual fields are commonly assessed by static perimetry. The basic form of this assessment involves sequentially presenting small test stimuli to each of a preset ensemble of locations across the visual field. During the test subjects indicate subjectively whether or not they have seen each test stimulus that they have been presented with whilst they maintain their gaze on a fixation target for the duration of the test. For most perimeters, subjects provide behavioural responses, such as button presses, to indicate when they have seen a particular test stimulus. Component parts of the visual field can have characteristic visual abilities. The goal of perimetry is thus to assess the visual ability or abilities of each part of the measured portion of the visual field.
Unrelated technologies are used to assess properties of the pupils of the eye, for example, devices that measure the static size of the pupil under particular viewing conditions are referred to as pupillometers and devices that monitor the changing size of pupils of time are referred to as pupillographs, and the distinctions between such devices are outlined by the USA Food and Drug Administration. Pupillographs have previously been used in conjunction with standard perimetry stimuli to measure responses to those stimuli and provide perimetric maps of the visual fields, however, these systems have proved to be unreliable and have not achieved commercial form or acceptance.
There are many reasons to assess the visual fields. For example the visual fields are fundamentally limited by physical features of the face such as the nose, brow ridges, and cheek bones, which change during development. Therefore, assessing the visual fields can be useful for tracking facial development or examining if a normal person's facial features provide them with a suitable visual field, for example, for use in certain sports or occupations. The visual nervous system continues to develop until adulthood and this can affect aspects of the visual field. Therefore, visual field testing can be used to determine the state of a young person's development. Physiological stress testing can also reversibly alter the visual fields. Therefore, the availability of a rapid means to test the visual fields before during and after the stress test is beneficial for stress level assessment. Visual field testing can also be useful in the management of disease rather than assisting in diagnosis per se. For example, persons with diseases such as multiple sclerosis can have periodic losses of vision due to transient conditions such as optic neuritis. The optic neuritis often resolves quickly but this can be aided by treatment. Visual field testing can therefore be used to assist in the management of such problems.
Similarly other diseases, such as glaucoma, can cause localised damage to smaller areas of the visual field. Again these diseases are amenable to current, and presumably future, treatments so visual field testing is useful to determine the effectiveness of treatment over time. Of course, this means visual field testing can be useful in providing data that would assist a physician, in conjunction with other data, to make a diagnosis of a disease such as glaucoma or other disease which affects the visual function of the subject. In the case of glaucoma, other data that would assist to confirm glaucoma, once a visual field defect had been observed with field testing, would include: eye pressure tests, measurement of the thickness of the nerve fibre layer of the retina by means of polarimetry or optical coherence tomography (OCT), and or the topography of the head of the optic nerve, often called the optic disc, by visual inspection, stereo fundus photography, OCT or confocal microscopy. These would normally be performed in conjunction with other tests such as magnetic resonance imaging, positron emission spectroscopy of the brain or electroencephalography, to eliminate brain related sources of the visual field defect such as stroke.
The primary drawback with existing static perimeter systems, however, is the subjective nature of the testing which causes the tests to suffer from inaccuracies and human/patient error since the current tests rely on the patient's ability to respond behaviourally to their detection of a stimulus (static perimeters do not use pupillary responses). Typically, the patient has a limited window of time in which to respond to the stimulus, and is presented with a limited number of stimuli. Therefore, if the patient is not concentrating some false positive or false negative responses will be delivered and the perimetry device will not be able to establish visual sensitivity well, thus compromising the accuracy of the diagnosis. The test may also be compromised by the patient's inability, or lack of desire as in cases of malingering, to respond to the stimulus accurately which may be caused by any number of variables for example whether the patient suffers from autism, age-related disorders, and drug impairment or intoxication to name a few.
A further disadvantage of current tests is the time in which a test may be completed. Since the patient must respond subjectively to each stimulus, this places a limit on the time in which the test may be conducted.
An objective alternate method for mapping the visual fields is to employ so-called multifocal methods. In these methods one uses an ensemble of visual stimuli, each member of the ensemble being presented to a particular sub-region of the visual field. The appearance or non-appearance of stimuli at each sub-region of the visual field is modulated by aperiodic pseudorandom temporal sequences that are mutually statistically independent. Optimally the modulation sequences should be completely statistically independent, that is the modulation sequences should be mutually orthogonal, which is to say having zero mutual correlation. A variety of patents related to various orthogonal (U.S. Pat. No. 5,539,482 to Maddess & James, the disclosure of which is wholly incorporated herein by cross-reference) and near orthogonal sequences (for example U.S. Pat. No. 4,846,567 to Sutter) exist, but recent analysis methods permit more general stimuli to be used (for example U.S. Pat. No. 6,315,414, U.S. Pat. No. 7,006,863 and International Patent Publication No. WO 2005/051193, all to Maddess & James, the disclosures of which are wholly incorporated herein by cross-reference).
The basic idea of multifocal methods is that the temporal statistical independence of the stimuli permits many stimuli to be presented concurrently, for example at different locations in the visual field, or different stimulus conditions, each driven by its own sequence. Then the estimated responses to presentations at all the test locations, or stimulus conditions, may be recovered from recordings of neural activity of the visual nervous system. The neural responses to the stimuli can be recorded by electrical or magnetic detectors, changes to the absorption, scattering or polarization infrared light or other electromagnetic radiation from parts of the nervous system, or functional magnetic resonance imaging. As can be appreciated, sensors for detection of such neural responses are complex and rely on correct placement for efficient operation, typically on the scalp of the patient. Also, methods such as electroencephalography suffer from the fact that different subjects have different brain anatomy and this affects the signals measured on the scalp. Subjects are also often averse to the placement of electrodes on their scalp or eyes, and there are health risks associated with any such contact method. Responses to the stimuli may be detected through monitoring of the pupils, which have the advantage of permitting non-contact assessment, however to date there are no commercial perimetry systems that use pupillography.
Accordingly, there is a need for a rapid objective, non-contact visual field assessment, which can be used for a variety of purposes, not just the assessment of the visual field of a subject, for example visual accommodation, visual acuity, hearing and audio-visual function, emotional state, drug use and mental health.
It is an object of the present invention therefore to substantially overcome or at least ameliorate one or more of the disadvantages of the prior art, or at least to provide a useful alternative, particularly when it is desirable to test an ensemble of stimuli (eg, visual, auditory or other stimulus detectable via a pupillary response) concurrently.